| Summary: | Objective To investigate the reparative role of dexmedetomidine (Dex) in lung injury secondary to acute kidney injury (AKI). Methods A total of 75 healthy SPF male C57BL/6J mice (6-8 weeks old, weighing 20-22 g) were randomly divided into Sham group (standard laparotomy), renal ischemia reperfusion group (RIR, clamping of bilateral renal pedicles for 50 min followed by reperfusion), and Dex pretreatment group (Dex+RIR, intraperitoneal injection of 25 μg/kg Dex 15 min before bilateral renal pedicle clamping). Lung tissues, bronchoalveolar lavage fluid (BALF), and carotid arterial blood samples were collected from 5 mice in each group at 24, 48, 72, 96, and 120 h after modeling. Lung injury and repair, arterial blood partial pressure of oxygen (PaO2), and BALF contents of transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) were observed and detected for comparison in the groups at different time points. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the transcript levels of interleukin-6(IL-6) and lung surfactant protein C (SP-C). Results Within 48 h after AKI, lung injury score was increased and PaO2 was decreased in the RIR group and Dex+RIR group than the Sham group, but Dex pretreatment reversed the lung injury score and PaO2 level when compared with the RIR group. The lung injury score was still in a high level and PaO2 stayed low in the RIR group within 96 h after AKI, whereas the 2 indicators in the Dex+RIR group showed a sustained improvement in 48 h after injury. After AKI, the BALF contents of TGF-β1 and CTGF and mRNA level of IL-6 in lung tissue showed a decreasing trend from high level to low level in the RIR group, but all of them were significantly higher than those in the Sham group (P < 0.05), while Dex intervention resulted in an obvious decrease of TGF-β1 at 24-120 h (P < 0.01) and a notable reduction of IL-6 mRNA level at 24-72 h (P < 0.05), whereas a raising trend and maintenance of high level in CTGF at 48-96 h. After AKI, the mRNA level of SP-C in the RIR group were up-regulated at 24 h (P < 0.001, when compared to the Sham group) and then diminished to a low level at 48-120 h (P < 0.05, when compared to the RIR group at 24 h), however Dex pretreatment could alleviate the transcriptional repression of SP-C caused by AKI. Conclusion Dex can ameliorate pulmonary ventilation after lung injury secondary to AKI, and then advance the time for lung repair from 96-120 h to 48-72 h.
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